CFTR mRNA compositions and related methods and uses

Patent metadata

Field	Value
Publication number	US-12594295-B2
Application number	US-202218049210-A
Country	US
Kind code	B2
Filing date	Oct 24, 2022
Priority date	Mar 14, 2013
Publication date	Apr 7, 2026
Grant date	Apr 7, 2026

Abstract

Materials, formulations, production methods, and methods for delivery of CFTR mRNA for induction of CFTR expression, including in the mammalian lung are provided. The present invention is particularly useful for treating cystic fibrosis.

First claim

We claim:

1 . A pharmaceutical composition comprising an mRNA-loaded nanoparticle,
wherein the mRNA is an in vitro transcribed mRNA, wherein the coding sequence of the mRNA is at least 95% identical to SEQ ID NO: 9, and wherein the mRNA encodes a human cystic fibrosis transmembrane conductance regulator (CFTR) protein comprising the amino acid sequence of SEQ ID NO: 1.

2 . The pharmaceutical composition of claim 1 , wherein the coding sequence of the mRNA is at least 98% identical to SEQ ID NO: 9.

3 . The pharmaceutical composition of claim 1 , wherein the coding sequence of the mRNA is set forth by SEQ ID NO: 9.

4 . The pharmaceutical composition of claim 1 , wherein the mRNA comprises a 5′ untranslated region (UTR) and/or a 3′ UTR.

5 . The pharmaceutical composition of claim 4 , wherein the 5′-UTR comprises SEQ ID NO: 4 and/or the 3′-UTR comprises SEQ ID NO: 5.

6 . The pharmaceutical composition of claim 4 , wherein the mRNA further comprises a poly-A tail.

7 . The pharmaceutical composition of claim 4 , wherein the mRNA further comprises a 5′ cap.

8 . The pharmaceutical composition of claim 1 , wherein the mRNA comprises at least one nonstandard nucleobase.

9 . The pharmaceutical composition of claim 8 , wherein the nonstandard nucleobase is chosen from one or more of 5-methyl-cytidine, pseudouridine, and 2-thio-uridine.

10 . The pharmaceutical composition of claim 1 , wherein the composition is formulated to be administered to the lung by aerosolization.

11 . The pharmaceutical composition of claim 10 , wherein the composition is formulated to be administered to the lung by nebulization.

12 . The pharmaceutical composition of claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier.

13 . The pharmaceutical composition of claim 1 , wherein the nanoparticle comprises one or more organic cations.

14 . The pharmaceutical composition of claim 13 , wherein the one or more organic cations are selected from the group consisting of polyethyleneimine (PEI), protamine, PEGylated protamine, poly-L-lysine (PLL), PEGylated PLL, a cationic lipid and combinations thereof.

15 . The pharmaceutical composition of claim 1 , wherein the nanoparticle comprises a polymer.

16 . The pharmaceutical composition of claim 15 , wherein the polymer comprises branched PEI with a molecular weight ranging from 10 kDa to 40 kDa.

17 . The pharmaceutical composition of claim 1 , wherein the nanoparticle is a liposome.

18 . A method of inducing CFTR expression in epithelial cells in a lung of a mammal, wherein the method comprises contacting the epithelial cells in the lung of the mammal with the composition of claim 1 .

19 . A nebulization or aerosolization apparatus comprising the pharmaceutical composition of claim 1 .

Assignees

• Translate Bio Inc
• Ethris Gmbh

Inventors

• Heartlein Michael
• Guild Braydon Charles
• Derosa Frank
• Rudolph Carsten
• Plank Christian
• Smith Lianne

Classifications

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title

• C12Y306/03049

  Channel-conductance-controlling ATPase (3.6.3.49) · CPC title

• C12N9/14

  Hydrolases (3) · CPC title

• A61K9/1271

  Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) · CPC title

• A61K9/0073

  Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; (nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M) · CPC title